Idiopathic chronic constipation: tachykinins as cotransmitters in colonic contraction

Mitolo‐Chieppa, D.; Mansi, G.; Nacci, Carmela; Salvia, Maria Antonietta De; Montagnani, Monica; Potenza, Maria Assunta; Rinaldi, Rosanna; Lerro, G.; Siro-Brigiani, G; Mitolo, C. I.; Rinaldi, Marcella; Altomare, D. F.; Memeo, V.

doi:10.1046/j.1365-2362.2001.00810.x

Cited by 34 publications

(30 citation statements)

References 20 publications

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“…Conversely, increased NO synthase-positive neurons and activities are associated with STC (Tomita et al, 2002;Wattchow et al, 2008). Our result is in agreement with the study by Mitolo-Chieppa et al (2001) performed in male STC circular muscle, which shows that EFS-induced relaxation of SP-precontracted muscle strips is reduced at 0.5 Hz (ATP mediated) and enhanced at 4 Hz (NO) medicated compared with control, suggesting an abnormality in NO and ATP release. Therefore, we cannot rule out that the reduced contractile amplitudes at higher frequency may be attributed to (or partially attributed to) the excessive NO production in STC.…”

Section: Discussionsupporting

confidence: 92%

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK₁ Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

Liu

Shang²,

Morgan³

et al. 2009

J Pharmacol Exp Ther

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Tachykinins are important neurotransmitters regulating intestinal motility. Slow transit constipation (STC) represents an extreme colonic dysmotility with unknown etiology that predominantly affects women. We examined whether the tachykinin system is involved in the pathogenesis of STC. Isolated sigmoid colon circular muscle from female STC and control patients was studied using functional and quantitative reverse transcriptase-polymerase chain reaction methods. A possible alteration of neurotransmission was investigated by electrical field stimulation (EFS) and ganglionic stimulation by dimethylphenylpiperazinium (DMPP). Substance P (SP)-mediated contractions in circular muscle strips were significantly diminished in STC compared with age-matched control (P Ͻ 0.001). In contrast, contractile responses to neurokinin A, the selective tachykinin NK 2 receptor agonist, [Lys to SP in STC were fully restored by indomethacin, partially reversed by tetrodotoxin (TTX), but unaffected by atropine or hexamethonium. The restoration by indomethacin was blocked by the NK 1 receptor antagonist CP99994 [(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] and TTX. In STC colonic muscle, there was a significant increase of NK 1 receptor mRNA expression, but no difference in NK 2 mRNA level. DMPP generated biphasic responses, relaxation at lower and contraction at higher concentrations. Although the responses to DMPP were similar in STC and control, an altered contractile pattern in response to EFS was observed in STC circular muscle. In conclusion, we postulate that the diminished contractile response to SP in STC is due to an increased release of inhibitory prostaglandins through activation of up-regulated NK 1 receptors. Our results also indicate some malfunction of the enteric nervous system in STC.

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Section: Discussionsupporting

confidence: 92%

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK₁ Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

Liu

Shang²,

Morgan³

et al. 2009

J Pharmacol Exp Ther

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“…The specimens were then subjected to transmural stimulation (EFS) at frequencies of 1, 3, 5, 10 Hz (15 V, 1 msec, pulse trains lasting 15 sec) through two parallel platinum electrodes connected to a stimulator (Digital Stimulator, LE 12106, Letica, Ugo Basile, Italy). The EFS induces an immediate relaxation of specimens followed, at the end of EFS, by a contraction called off contraction [12]. Therefore, we evaluated all components of the inhibitory responses obtained after EFS, that is, (a) area under the curve (AUC), expressed as percentage of the maximal effect elicited by sodium nitroprussiate (SNP) since at the end of each evaluation curve, specimens were stimulated with SNP (50 μ M); (b) the minimum value of basal tone reached during inhibitory response; (c) the off-contraction (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Hemin and Zinc Protoporphyrin IX Affect Granisetron Constipating Effects In Vitro and In Vivo

Zigrino

Leo

Renna

et al. 2013

ISRN Gastroenterology

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Granisetron is a 5-HT3 receptors antagonist used in the management of emesis associated with anticancer chemotherapy. It affects intestinal motility with constipating effect. Since the pathway heme oxygenase/carbon monoxide (HO/CO) is involved in gastrointestinal motility, we evaluated the possible interplay between granisetron and agents affecting HO/CO pathways such as zinc protoporphyrin IX (ZnPPIX), an HO inhibitor, or hemin, an HO-1 inducer. ZnPPIX (10 µM) or hemin (10 µM), but not granisetron (0.1, 0.3, 1 µM), affected spontaneous basal activity recorded in rat duodenal strips, in noncholinergic nonadrenergic conditions. Granisetron restored spontaneous basal activity after ZnPPIX, but not after hemin. ZnPPIX decreased and hemin increased the inhibition of activity after electrical field stimulation (EFS), but they did not affect the contraction that follows the relaxation induced by EFS called off contraction. Granisetron did not alter the response to EFS per se but abolished both ZnPPIX and hemin effect when coadministered. In vivo study showed constipating effect of granisetron (25, 50, 75 µg/kg/sc) but no effect of either ZnPPIX (50 µg/kg/i.p.) or hemin (50 µM/kg/i.p.). When coadministered, granisetron effect was abolished by ZnPPIX and increased by hemin. Specimens from rats treated in vivo with hemin (50 µM/kg/i.p.) showed increased HO-1 protein levels. In conclusion, granisetron seems to interact with agents affecting HO/CO pathway both in vitro and in vivo.

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“…It is well known that the rebound contractile response is reduced by administration of atropine and TK antagonists [13], indicating that nerve stimulation mainly involves the corelease of ACh and TKs [14]. In order to evaluate whether the contribution of ACh and TKs to the 'off-contraction' is altered by in vivo treatment with ILs, preparations were incubated for 10 min with atropine and NK 2 antagonist.…”

Section: Excitatory Neurotransmissionmentioning

confidence: 99%

Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: an in vitro study

Natale

Piepoli²,

Salvia

et al. 2003

Eur J Clin Investigation

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Idiopathic chronic constipation: tachykinins as cotransmitters in colonic contraction

Abstract: We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK2 and NK3 receptor agonists.

Cited by 34 publications

References 20 publications

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK₁ Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK₁ Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

Hemin and Zinc Protoporphyrin IX Affect Granisetron Constipating Effects In Vitro and In Vivo

Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: an in vitro study

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Idiopathic chronic constipation: tachykinins as cotransmitters in colonic contraction

Abstract: We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK2 and NK3 receptor agonists.

Cited by 34 publications

References 20 publications

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK1 Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK1 Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

Hemin and Zinc Protoporphyrin IX Affect Granisetron Constipating Effects In Vitro and In Vivo

Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: an in vitro study

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Product

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Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK₁ Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK₁ Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation